Abstract

Thymic epithelial cells (TECs) are the predominant intrathymic source of the essential thymopoietin IL-7. Whether thymocyte-TEC interactions have a role in the regulation of IL-7 expression is not known. By exploiting IL-7 reporter mice in which yellow fluorescent protein expression identifies TECs expressing high levels of IL-7 (Il7+ TECs), we show that Il7+ TECs segregate from emerging medullary TECs during thymic organogenesis. Although Il7+ TECs normally diminish with age, we found that Il7+ TECs are markedly retained in alymphoid Rag2−/−Il2rg−/− IL-7 reporter mice that manifest a profound thymopoietic arrest. Transfer of Tcra−/− or wild-type (but not Rag2−/−) hematopoietic progenitors to alymphoid IL-7 reporter recipients normalizes the frequency of Il7+ TECs and re-establishes cortical TEC/medullary TEC segregation. Although thymocyte-derived signals are often considered stimulatory for TEC maturation, our findings identify a negative feedback mechanism in which signals derived from TCRβ-selected thymocytes modulate TEC-dependent IL-7 expression.

Footnotes

This work was supported in part by Institut Pasteur, Institut National de la Santé et de la Recherche Médicale, the Fondation pour le Recherche Médicale (SPF20081214865), the Ligue Nationale Contre le Cancer, and the Foundation for Science and Technology (SFRH/45932/2008 and Program Ciência 2008).